Microprost

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MIPROPROST (MICROPROST)

Composition:

Active substance: travoprost;

1 ml of solution contains 0.04 mg of travoprost;

Excipients: zinc chloride, hydrogenated castor oil (polyoxyl 40), boric acid, propylene glycol, sorbitol (Neosorb 70/20 B), sodium hydroxide and/or hydrochloric acid (for pH adjustment), water for injections.

Pharmaceutical form. Eye drops.

Main physicochemical properties: clear, colorless or pale yellow solution, practically free from particles.

Pharmacotherapeutic group. Agents used in ophthalmology. Anti-glaucoma preparations and miotics. Prostaglandin analogues.

ATC code S01E E04.

Pharmacological Properties

Pharmacodynamics. Travoprost, a prostaglandin F2α analog, is a full selective agonist of the prostaglandin FP receptor, with a high degree of affinity for FP receptors. It reduces intraocular pressure by increasing the outflow of aqueous humor through the trabecular meshwork and uveoscleral pathway. The exact mechanism of action is not fully understood.

Pharmacokinetics. Travoprost is absorbed through the cornea, where it is hydrolyzed to the active free acid. Data from 4 multiple-dose pharmacokinetic studies (in total involving 107 subjects) showed that the concentration of the free acid in plasma was below 0.01 ng/mL (the quantitative limit of analysis) in two-thirds of subjects. In individuals with measurable plasma concentrations (N = 38), the mean plasma Cmax was 0.018 ± 0.007 ng/mL (range: 0.01 to 0.052 ng/mL), reached within 30 minutes. According to these studies, travoprost has a plasma half-life of 45 minutes. There was no difference in plasma concentrations between day 1 and day 7, indicating that steady state was achieved early and there was no significant accumulation.

Metabolism is the major route of elimination for both travoprost and its active free acid.

Systemically, the free acid of travoprost is metabolized to inactive metabolites via β-oxidation of the α-chain (carboxylic acid) forming 1,2-dinor and 1,2,3,4-tetranor analogs, as well as via oxidation of the 15-hydroxyl moiety and reduction of the 13,14 double bond.

The free acid of travoprost and its metabolites are primarily excreted by the kidneys. Elimination of the free acid of travoprost from plasma is rapid, and levels are typically below the quantifiable limit within one hour after dosing. The terminal half-life of the free acid of travoprost was estimated in fourteen subjects and ranged from 17 to 86 minutes, with a mean half-life of 45 minutes. Less than 2% of the topically administered dose of travoprost is excreted in urine within 4 hours as the free acid of travoprost.

Clinical characteristics

Indications. To reduce elevated intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma.

Contraindications. Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction. Studies on interaction with other medicinal products have not been conducted.

Specific in vitro interaction studies were conducted using travoprost and thimerosal-containing preparations. No evidence of precipitation was observed.

Special precautions for use

Pigmentation

Ophthalmic travoprost solution has been reported to cause pigmentation of ocular tissues. Increased pigmentation of the iris, periorbital area (eyelids), and eyelashes has been most frequently reported. The pigmentation increases as long as travoprost is administered. The pigmentation is due to increased melanin content in melanocytes, rather than an increase in the number of melanocytes. After discontinuation of travoprost, iris pigmentation is likely to be permanent, whereas pigmentation of the periorbital area and changes in the eyelash area may be reversible in some patients. Patients using Travoprost should be informed about the possibility of increased pigmentation. The long-term effects of increased pigmentation are unknown.

The change in iris color may not be noticeable for several months or years. Typically, brown pigmentation starts around the pupil and spreads concentrically toward the periphery of the iris of the treated eye; however, the entire iris or parts of it may become more intensely brown. No changes in iris nevi or freckles have been observed during therapy. Treatment may be continued if a noticeable change in iris pigmentation occurs, but patients should undergo regular examinations.

Changes in eyelashes

Travoprost may gradually alter the structure of eyelashes and vellus hair of the treated eye. Such changes include increased length, thickness, and number of eyelashes. Eyelash changes are usually reversible and disappear after discontinuation of travoprost treatment.

Ocular inflammation

Travoprost should be used with caution in patients with ocular inflammatory conditions, such as uveitis, as inflammation may be exacerbated.

Angle-closure glaucoma, inflammatory or neovascular glaucoma

There is no experience with the use of travoprost in angle-closure, inflammatory, or neovascular glaucoma.

Macular edema

Macular edema, including cystoid macular edema, has been reported during treatment with travoprost solution.

Caution is recommended when prescribing Travoprost to patients with aphakia, pseudophakia, posterior capsule rupture, anterior chamber lenses, or other risk factors for macular edema.

Bacterial keratitis

Bacterial keratitis has been associated with the use of multi-dose containers for topical ophthalmic products. These containers were inadvertently contaminated by patients, most of whom had concurrent corneal disease or disruption of the ocular epithelial surface.

Use in elderly patients

Overall, no clinically significant differences in safety and efficacy have been observed between elderly patients and other adult patients.

Excipients

Travoprost contains propylene glycol, which may cause skin irritation.

Contains hydrogenated castor oil, which may cause skin reactions.

Contact lenses

Patients must remove contact lenses before instilling the medicinal product and wait 15 minutes after instillation before reinserting contact lenses.

Use during pregnancy or breastfeeding

Pregnancy

There are no adequate and well-controlled studies in pregnant women regarding the risk associated with the use of the drug.

In animal studies, subcutaneous administration of travoprost at clinically relevant doses to pregnant mice and rats during the period of organogenesis resulted in embryofetal mortality, spontaneous abortions, and premature delivery.

Pregnant women should be informed of the potential risk to the fetus. Since reproductive studies in animals do not always predict human response, Travoprost should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The baseline risk of major congenital malformations and miscarriage in the indicated population is unknown; however, in the general U.S. population, the estimated background risk of major congenital malformations is 2–4%, and of miscarriage is 15–20% of clinically recognized pregnancies.

Breastfeeding

It is unknown whether travoprost from ophthalmic drops passes into human breast milk. Animal studies have shown that travoprost and its metabolites can be excreted in breast milk; therefore, Travoprost is not recommended during breastfeeding.

Ability to influence the speed of reactions when driving or operating machinery.
Travoprost has no effect or has a negligible effect on the ability to drive or operate machinery. However, as with any ophthalmic drops, transient blurred vision or other visual disturbances may affect this ability. If blurred vision occurs after instillation, patients should wait until vision clears before driving or operating machinery.

Method of Administration and Dosage

For ophthalmic use.

Instill one drop of Microprost into the affected eye(s) once daily in the evening.

It should not be used more frequently than once daily, since more frequent administration of prostaglandin analogs has been shown to reduce the intraocular pressure (IOP)-lowering effect.

Reduction of IOP begins approximately 2 hours after the first dose, with maximum effect occurring at 12 hours.

Microprost may be used concomitantly with other ophthalmic solutions for IOP reduction. In this case, the eye drops should be administered at least 5 minutes apart.

If a dose is missed, treatment should continue with the next scheduled dose. The duration of treatment is determined by the physician.

• Wash hands before instillation.
• Remove the dropper bottle from the packaging. Open the bottle immediately before use. After first opening, record the date of opening on the carton.
• Hold the bottle with the dropper tip pointing downward between the thumb and index finger.
• Tilt the head backward. Gently pull down the lower eyelid with a clean finger to create a "pocket" between the eyelid and the eye, into which the drop will be instilled.
• Bring the dropper tip close to the eye. If convenient, do this in front of a mirror.
• Do not touch the dropper tip to the eye, eyelid, surrounding areas, or any other surfaces to avoid contaminating the solution in the bottle.
• Gently squeeze the bottle to release one drop.
• After instilling Microprost eye drops, press with a finger at the inner corner of the eye near the nose for at least one minute. Keep the eyelid closed. This helps prevent the medication from draining into the nose and reduces systemic absorption.
• If instilling drops into both eyes, repeat the procedure for the other eye.
• Immediately after use, tightly screw the cap back onto the bottle.

If the drop misses the eye, try again.

Do not use the medicinal product in any way other than as recommended by the physician.

Use in Hepatic and Renal Impairment

The use of travoprost has been studied in patients with hepatic impairment (mild to severe) and in patients with renal impairment (mild to severe) (creatinine clearance below 14 mL/min). In these patients, no clinically significant changes were observed in hematology, blood biochemistry, or urine laboratory parameters. Dose adjustment is not required in these patients.

Children. Travoprost is not recommended for use in children under 16 years of age due to potential safety concerns related to increased pigmentation following long-term use.

Overdose. There have been no reports of overdose. If an excessive amount of the medicinal product enters the eye, rinse the eye with warm water. In case of accidental ingestion, symptomatic and supportive therapy should be administered.

Adverse Reactions

The most common adverse reactions during clinical studies and the post-marketing period of the medicinal product were ocular hyperemia and increased pigmentation of the iris.

Listed below are the adverse reactions categorized by organ systems. Frequency of occurrence is defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), unknown (cannot be estimated from available data). Within each group, adverse effects are listed in order of decreasing severity.

Reporting of suspected adverse reactions

Reporting of adverse reactions following marketing authorization of a medicinal product is of great importance. It allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 24 months.

After opening the bottle, store no longer than 28 days.

Storage conditions. Store at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 5 ml in a dropper bottle; 1 dropper bottle per cardboard box.

Prescription status. Prescription only.

Manufacturer. Micro Labs Limited.

Manufacturer's address and site of operations

Plot Nos. 113-116, Phase IV, KIADB, Bommansandra Industrial Area, Jigani Link Road, Anekal Taluk, Bangalore 560 099, India.